Pulmonary Gas Exchange Lecture Notes PDF

Pulmonary Gas Exchange Damsara Nandadeva MBBS, MPhil, PhD Senior Lecturer Department of Physiology Faculty of Medicine Peradeniya  Objectives Define the terms “partial pressure” and “fractional concentration”. List the normal fractional concentrations and sea level part...

Pulmonary Gas Exchange Damsara Nandadeva MBBS, MPhil, PhD Senior Lecturer Department of Physiology Faculty of Medicine Peradeniya  Objectives Define the terms “partial pressure” and “fractional concentration”. List the normal fractional concentrations and sea level partial pressures for O2, CO2, and N2. Explain O2 and CO2 composition of alveolar gases. State the alveolar and blood gas pressures and discuss the factors that determine alveolar gas pressure. Describe the process of gas exchange at the lungs in terms of the respiratory membrane, factors affecting gas exchange, role of diffusion and diffusing capacity. Explain the oxygen cascade  Objectives At the end of this lecture, you should not feel like it was a mistake to do medicine!!  Gas exchange 2nd step in the process of “respiration” Pulmonary Movement of O2 from alveoli to blood ventilation Movement of CO2 from blood to alveoli External 4th step in the process of “respiration” respiration Movement of O2 from blood to tissues Movement of CO2 from tissues to blood Transport of gases Occurs by the process of diffusion Internal respiration  Basic properties of gases Partial pressure (P) = the pressure that a gas in a mixture of gases would exert if it occupied the same volume as the mixture Directly proportional to the concentration of the gas molecules (No of moles in a given volume) Dalton’s law Sum of the partial pressure in a mixture of gases will equal the total pressure Ptotal = PA + PB + PC  Partial pressure of gases in inspired air Total atmospheric pressure at sea level (Patm) = 760 mmHg Patm = PN2 + PO2 + PCO2 + Pother Calculating a partial pressure of a gas = fraction (percentage) of the gas present in a mixture of gases × total pressure of the gas mixture Fraction of O2 (FiO2) in dry atmospheric air (inspired air) at sea level = 0.21 or 21% Fraction of N2 in inspired air at sea level = 0.79 or 79% Fraction of CO2 in inspired air at sea level = 0.0004 or 0.04%  Partial pressure of gases in inspired air Partial pressure of O2 (PO2) in inspired air at sea level = 760 mmHg × 0.21 = 159.6 ~ 160 mmHg Calculate the partial pressure of CO2 and N2 in inspired air at sea level Partial pressure of gases in humidified air Once air is inhaled → gets humidified in the upper airway by mixing with water vapor Water molecules that escape into the gas phase exert a pressure → water vapor pressure PH2O at body temperature when 100% humidified = 47 mmHg Partial pressure of gases in humidified air Since total pressure is constant, partial pressure of other gases reaching the lungs is reduced (all other gases are diluted) PO2 of 100% humidified air (airways) = (760 – 47)mmHg × 0.21 ~ 150 mmHg PCO2 of 100% humidified air (airways) = (760 – 47) mmHg × 0.0004 ~ 0.3 mmHg  Composition of alveolar air Composition of alveolar air is different from inspired air because Atmospheric air is humidified in the upper airway Alveolar air is only partially replaced by atmospheric air with each breath Why? O2 is constantly absorbed into pulmonary capillary blood from alveoli CO2 is constantly added to alveoli from pulmonary capillary blood  Partial pressure of gases in alveolar air O2 concentration in the alveoli depends on Rate of diffusion of O2 from alveoli to blood = tissue O2 consumption Rate of entry of new O2 into alveoli = rate of alveolar ventilation Normal rate of O2 diffusion High rate of O2 diffusion e.g., exercise  Partial pressure of gases in alveolar air CO2 concentration in the alveoli depends on Rate of CO2 delivery to alveoli = rate of CO2 production in tissues Rate of removal of CO2 from alveoli = rate of alveolar ventilation  Partial pressure of O2 in alveolar air Partial pressure of O2 in alveolar air (PAO2) can be calculated using the alveolar gas equation PAO2 = (PB – PH2O) × FiO2 – (PACO2/R) PB = barometric pressure = 760 mmHg at sea level PH2O = water vapor pressure at body temperature = 47 mmHg FiO2 = fraction of O2 in inspired air = 21% PACO2 = Partial pressure of CO2 in alveoli = 40 mmHg R = respiratory quotient = 0.8  Respiratory Quotient Ratio of the volume of CO2 produced to O2 consumed per minute Gives an estimate of the rate of flow of CO2 and O2 molecules across the respiratory membrane Depends on the substrates used in internal respiration CHO → R = 1.0 Fats → R ~ 0.7 Proteins → R ~ 0.8 Mixed diet → R = 0.8 Volume of CO2 produced per min = 200/250 = 0.8 Volume of O2 consumed per min  Partial pressure of O2 in alveolar air PAO2 = (PB – PH2O) × FiO2 – (PACO2/R) PAO2 at sea level = (760 – 47) mmHg × 0.21 – (40mmHg/0.8) = 99.7 ~ 100 mmHg  Partial pressure of gases in expired air Expired air is a combination of dead space air and alveolar air Partial pressure of gases are in between those of humidified air and alveolar air  PO2= 160 mmHg PCO2 = 0.3 mmHg PO2= 100 mmHg PCO2 = 40 mmHg PO2= 40 mmHg PO2= 100 mmHg PCO2 = 46 mmHg PCO2 = 40 mmHg PO2~ 40 mmHg PCO2 ~ 46 mmHg Diffusion of gases through the respiratory membrane  Respiratory membrane (Alveolar capillary membrane) Formed of 1. Layer of fluid lining the alveolus (contain surfactant) 2. Alveolar epithelium 3. Epithelial basement membrane 4. Thin Interstitial space 5. Capillary basement membrane 6. Capillary endothelium Average thickness: 0.6 µm Total surface area~ 70 m2  Gas exchange at the lungs Occurs via simple diffusion across the respiratory membrane  Diffusion of gases through respiratory membrane Factors affecting rate of diffusion (Fick’s law) 𝐷 × ∆𝐶 × 𝐴 𝑁𝑒𝑡 𝑟𝑎𝑡𝑒 𝑜𝑓 𝑑𝑖𝑓𝑓𝑢𝑠𝑖𝑜𝑛 = 𝑇 Vgas = rate of diffusion A = surface area of the membrane T = thickness of the membrane D = diffusion coefficient of the gas P1-P2 = partial pressure difference CO2 diffuses ~ 20 time more rapidly than O2 due to higher solubility  Factors affecting rate of diffusion Partial pressure gradient O2 CO2 P1 – P2 = 100 – 40 P1 – P2 = 46 – 40 = 60 mmHg = 6 mmHg Partial pressure gradient for O2 is reduced in Hypoxic environment (high altitude)  Factors affecting rate of diffusion Surface area of the membrane can be reduced in Emphysema Removal of one lung/lobectomy  Factors affecting rate of diffusion Thickness of the membrane can be increased in Pulmonary edema - fluid in the interstitial space of the lung and in the alveoli Lung fibrosis  Factors affecting rate of diffusion Diffusion coefficient 𝑆𝑜𝑙 𝐷= √𝑀𝑊 Solubility of CO2 is much higher than that of O2 CO2 diffuses ~ 20 times more rapidly than O2 despite a lower pressure gradient and not so different molecular weights  Gas laws Henry’s law Concentration of gas dissolved in a liquid is proportional to its partial pressure When a gas is in contact with liquid, gas dissolves in proportion to its partial pressure → gives the partial pressure of gas in the liquid phase Alveolar PO2 = 100mmHg → at equilibrium, PO2 in pulmonary capillary blood = 100mmHg  Diffusion and perfusion limitations Two main processes can limit the rate of alveolar-capillary gas transfer Properties of diffusion → diffusion-limited Perfusion (blood flow through the pulmonary capillaries) → perfusion-limited Whether the transfer of a gas is limited by properties of diffusion or by perfusion depends on the reactions of the gas with substances (e.g., Hb) in blood At rest, time taken for a blood to traverse the pulmonary capillaries = 0.75 sec  Diffusion-limited gas exchange Gas “A” – has a high affinity to Hb in red cells Gas “A” diffuses across the respiratory membrane into capillary blood and tightly binds with Hb in the red cell Minimal amount of gas “A” is dissolved in blood during the 0.75 sec Minimal rise in partial pressure of gas “A” in capillary blood Partial pressure gradient is maintained all along the capillaries (equilibrium not reached) Transfer of gas “A” will be limited by properties of diffusion and not perfusion  Diffusion-limited gas exchange Example of gas “A” at rest Carbon monoxide (CO) Even if perfusion rate is reduced (blood spends more time in pulmonary circulation) CO will continue to diffuse because of the partial pressure gradient. Transfer of CO will reduce if factors influencing diffusion are changed (e.g., increased thickness of membrane) Diffusion-limited gas exchange  Perfusion-limited gas exchange Gas “B” does not bind with any substance in blood Gas “B” diffuses across the respiratory membrane into capillary blood and dissolves in blood Partial pressure of gas “B” increases in capillary blood Equilibrium is reached before blood has flown through the pulmonary capillaries  Perfusion-limited gas exchange Example of gas “B” at rest Nitrous oxide (N2O) Amount of N2O transferred across the membrane is limited by the blood flow More N2O can be transferred across the membrane if blood flow is increased Perfusion-limited gas exchange O2 transfer across the respiratory membrane O2 (and CO2) transfer at rest in normal healthy lung Perfusion-limited O2 transfer may be diffusion- limited in diseases - thickening of respiratory membrane in pulmonary fibrosis Strenuous exercising at high altitude – reduced diffusion due to low partial pressure gradient  Diffusing capacity of the lungs (DL) Volume of a gas that will diffuse through the membrane each minute for a partial pressure difference of 1 mmHg DL = Vgas / PA – PC Diffusing capacity of the lung is measured using carbon monoxide since the gas is diffusion-limited Since Pc for CO is negligible, DLCO = VCO / PACO ~ 25 ml/min/mmHg DLCO is measured to assess the severity of lung diseases Need to correct for Hb concentration because …….?  Diffusing capacity for respiratory gases DLO2 at rest ~ 25ml/min/mmHg DLCO2 at rest ~ 400 ml/min/mmHg Diffusing capacity is increased during exercise  Oxygen Cascade Stepwise decrease in PO2 from atmospheric air to mitochondria Dry atmospheric 160 mmHg Tracheal air 150mmHg Humidification Dilution by CO2 Alveolar air 100 mmHg Pulmonary capillary ~ 100 mmHg Venous admixture Systemic arterial blood~ 92 mmHg Diffusion Tissue capillaries ~ 40 mmHg Diffusion Mitochondria ~ 1 mmHg  A-a gradient Alveolar to arterial O2 gradient A-a gradient = PAO2 – PaO2 Calculated using the Measured via alveolar gas equation arterial blood gas Normal A-a gradient for a young adult = 5 – 10 mmHg Increases with age Useful to determine the source of hypoxemia Causes of hypoxemia with high A-a gradient? Causes of hypoxemia with normal A-a gradient?